Structure of 53572-98-8
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 53572-98-8 |
Formula : | C6H4N2O2S |
M.W : | 168.17 |
SMILES Code : | O=C(C1=CN2C(SC=C2)=N1)O |
MDL No. : | MFCD03419463 |
InChI Key : | BAKIBSRDBASFAQ-UHFFFAOYSA-N |
Pubchem ID : | 2759354 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; | B.3 Synthesis of carboxylic amide derivatives (general procedure II); To a solution of the respective carboxylic acid (0.030 mmol, 1.8eq) in DMF (0.25 mL) is added successively a solution of DIPEA (0.075 mmol, 4.4eq) in DMF (0.15 mL) and a solution of TBTU (0.030 mmol, 1.8eq) in DMF (0.15 mL). The obtained mixture is treated with a solution of the respective 3-aza-bicyclo[3.1.0]hexane derivative (0.017 mmol, l.Oeq, free base) in DMF (0.15 mL). The mixture is shaken over night and purified by prep. HPLC to give the respective amide derivatives.Example 65: imidazo[2,l-b]thiazole-6-carboxylic acid [(lR*,2S*,5S*)-3-(2-methyl-5-m-tolyl- thiazole-4-carbonyl)-3-aza-bicyclo[3.1.0]hex-2-ylmethyl]-amide prepared by reaction of [(1R ,2S ,5S )-2-aminomethyl-3-aza-bicyclo[3.1.0]hex-3-yl]- (2-methyl-5-m-tolyl-thiazol-4-yl)-methanone with imidazo[2, 1 -b]thiazole-6- carboxylic acid. LC-MS: tR = 0.84 min; [M+H]+ = 478.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; | To a solution of the respective carboxylic acid (0.030 mmol, 1.8 eq) in DMF (0.25 mL) is added successively a solution of DIPEA (0.075 mmol, 4.4 eq) in DMF (0.15 mL) and a solution of TBTU (0.030 mmol, 1.8 eq) in DMF (0.15 mL). The obtained mixture is treated with a solution of the respective 3-aza-bicyclo[3.1.0]hexane derivative (0.017 mmol, 1.0 eq, free base) in DMF (0.15 mL). The mixture is shaken over night and purified by prep. HPLC to give the respective amide derivatives. prepared by reaction of [(1R*,2S*,5S*)-2-aminomethyl-3-aza-bicyclo[3.1.0]hex-3-yl]-(2-methyl-5-m-tolyl-thiazol-4-yl)-methanone with <strong>[53572-98-8]imidazo[2,1-b]thiazole-6-carboxylic acid</strong>. LC-MS: tR=0.84 min; [M+H]+=478.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20℃; | To a solution of 1 (0.25 g, 0.428 mmol) and Et3N (0.04 g, 0.428 mmol) in DMF (2 ml) was added a solution of HOBT (0.07 g, 0.428 mmol), HBTU (0.16 g, 0.428 mmol) and <strong>[53572-98-8]imidazo[2,1-b]thiazole-6-carboxylic acid</strong> (0.07 g, 0.428 mmol) in DMF (3ml). The resulting solution was allowed to stir overnight at rt. Purification by flash chromatography (Et3N/MeOH/EtOAc = 1/10/89) yielded protected intermediate which was taken directly to the next step without further characterization. Starting from the protected intermediate, CH3CN (2.5 ml), H2O (2.5 ml) and TFA (2 ml) was added to the reaction mixture. The resulting solution was allowed to stir overnight at rt. The volatiles were removed in vacuo and the reaction mixture was subjected to reverse phase chromatograph, followed by lyophilization yielding 5 as a white solid (0.19 g, 71%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; In N,N-dimethyl-formamide; | Example 10 (S)-N-(1-(3-(3-Chloro-4-cyano-5-fluorophenyl)-1H-pyrazol-1-yl)propan-2-yl)imidazo[2,1-b]thiazole-6-carboxamide The title compound was prepared using the procedure described in Example 3(h) starting from <strong>[53572-98-8]imidazo[2,1-b]thiazole-6-carboxylic acid</strong> (1.041 mmol, 0.175 g) and (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chloro-6-fluorobenzonitrile (1.041 mmol, 0.290 g). DMF (10 ml) was used as the solvent and the reaction time was 2 days. The work up was done by diluting the reaction mixture with water and ethyl acetate and washing it with 2M Na2CO3, water and brine. The combined organics were dried, filtered and eveaporated. The crude product was purified by flash chromatography. 0.186 g of the title compound was obtained. 1H-NMR (400 MHz, MeOH-d4): delta 1.24 (d, 3H), 4.32-4.39 (m, 1H), 4.40-4.47 (m, 1H), 4.53-4.61 (m, 1H), 6.79 (d, 1H), 7.20 (d, 1H), 7.73 (d, 1H), 7.76 (d, 1H), 7.77-7.81 (m, 1H), 7.89-7.91 (m, 1H), 8.10 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 23℃; for 16.0h; | General procedure: The fragment carboxylic acid (0.35 mmol) was dissolved in dimethylformamide (0.2 M, 1.75 mL), then 14 (42.6 mg, 0.35 mmol), HBTU (128 mg, 0.34 mmol), and HOBT (51.8 mg, 0.38 mmol) were added, followed by diisopropylethylamine (175 muL, 1.047 mmol). The reaction was stirred at 23 C for 16 h. TLC at 16 h showed conversion to product. The reaction was quenched with H2O (5 mL) and extracted with DCM (3 x 5 mL). The combined organic layers were washed with 1 M HCl (10 mL), saturated aqueous NaHCO3 (10 mL), and saturated aqueous NaCl (10 mL). The organic layer was dried over MgSO4, filtered, and evaporated. Purification with flash column chromatography with CH3OH/CH2Cl2 ( CH3OH gradient 0 ? 5 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Imidazo[2,i -b]thiazole-6-carboxylic acid (0.25 mmol), HATU (0.25 mmol) and DIPEA (0.5 mmol) were dissolved in acetonitrile (1 mE) and added to 5-amino-i-(3- tert-butoxycarbonylamino-i -propyl)benzimidazole (synthesis, see before; one entire batch was used) after 10 mm. The mixture was shaken overnight at room temperature, then the solvent was evaporated, the residue was dissolved in ethyl acetate and washed with aqueous citric acid (5%), aqueous sodium carbonate andwater and evaporatedto dryness. To the residue was added dichloromethane (2 mE), followed by trifluoroacetic acid, and the mixture was agitated for 30 mm at room temperature, whereupon the solvents were evaporated and the residue was purified by preparative reverse-phaseHPEC-MS. ESI-MS: 341 (M+i). |
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